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β, β-dimethylacrylshikonin exerts antitumor activity via Notch-1 signaling pathway in vitro and in vivo.
MedLine Citation:
PMID:  22634048     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
β,β-dimethylacrylshikonin(DA) is a major component of Radix Lithosperm erythrorhizon and has various biological activities. We have investigated the inhibitory effect of DA on the growth of hepatocellular carcinoma in vitro and in vivo. Notch signaling plays a critical role in maintaining the balance between cell proliferation, differentiation and apoptosis. Hence, perturbed Notch signaling may contribute to tumorigenesis. In the present study, we evaluated whether DA could be an effective inhibitor on cell growth in human gastric cancer cell line, and also the molecular mechanisms. Using multiple cellular and molecular approaches such as MTT assay, Colony formation assay, DAPI staining, Flow cytometry, Real-time PCR and Western blot analysis, we found that DA inhibited cell growth in a dose- and time-dependent manner. Biochemical analysis revealed the involvement of cell cycle regulated proteins in DA-mediated of G(0)-G(1) arrest of SGC-7901 cells. Furthermore, DA treatment led to reduced Notch-1 activation, expression of Jagged-1 and its downstream target Hes-1 in vitro and in vivo. Our data demonstrated that DA is a potent inhibitor of progression of gastric cancer cells, which could be due to attenuation of Notch-1. We also suggest that DA could be further developed as a potential therapeutic agent for the treatment of gastric cancer.
Authors:
Shao Zhen-Jun; Zhang Yuan-Yuan; Fan Ying-Ying; Jin Shao-Ju; Yan Jiao; Zheng Xiao-Wei; Chen Jian; Xiong Yao; Zhou Li-Ming
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-22
Journal Detail:
Title:  Biochemical pharmacology     Volume:  -     ISSN:  1873-2968     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
Affiliation:
Department of Pharmacology, Preclinical and Forensic Medical College, Sichuan University, Chengdu, 610041, China.
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